Autoimmunity is described as an immune response directed against an antigen within the body of the host. This definition is independent of whether the response is innate or acquired, and if acquired whether it is induced by a foreign or autochthonous antigen. In other words, if acquired, the response is induced by a foreign antigen or antigen found in the part of the body or locality in which it originates, such as that produced by a cancer. Autoimmunity usually involves both T-cell and B-cell responses in a three dimensional complex immunologic array. The primary requirement is an immune response directed to a self-antigen.
In dealing with human disease it is often difficult to establish causality. As such the diagnosis of an autoimmune disease may be established by direct evidence, indirect evidence or circumstantial evidence. Direct evidence usually involves the transfer of an antibody from a patient to a healthy recipient. Indirect evidence can be found in such disease states as: (a) the reproduction of disease in animals via immunization with a select antigen, (b) naturally occurring disease in animals resembling the human counterpart, and (c) disease created by manipulating the immune system. Circumstantial evidence, the lowest level of proof, is suggested by confirming the presence of autoantibodies. Another type of circumstantial evidence is identified from the finding that autoimmune diseases have a tendency to cluster, likely from defined or yet to be defined genetic susceptibility traits. From a pathological perspective, with few exceptions, all autoimmune diseases require the presence of self-reactive CD4 T lymphocytes.
A separate category of autoimmune diseases, the autoinflammatory diseases, exists in which there is no evidence of adaptive immunity in the form of self-reactive T cells. This latter group consists of a core of six disorders known as hereditary recurrent fever syndromes.
Clinically, physicians tend to categorize autoimmune diseases as systemic (such as in the case of systemic lupus erythematosis) or organ-specific (such as type I diabetes mellitus). Therapy has generally been directed to the specific disease and associated presentation. Four therapeutic approaches are usually employed, but the complex causes of the two categories of autoimmune disorders offer considerable challenges to the development of new therapies. Moreover, many of the current modalities—such as the immunomodulators, immunosuppressants, steroids, and intravenous gamma globulin, to name a few—precipitate side effects that are worse than the underlying disease.